Vioxx Settlement Puts Painkillers Back in the Spotlight

Mar. 23 -- FRIDAY, Nov. 9 (HealthDay News) -- With Friday's announcement of almost $5 billion to be paid out to those people claiming they were hurt by the now-withdrawn painkiller Vioxx, the drug's maker, Merck & Co., may have hoped to end the glare of publicity on these types of drugs.

But, according to experts, the move has merely swung the focus back on the medications once again.

Cox-2 inhibitor drugs such as Vioxx, Bextra and Celebrex were initially hailed as a means of treating pain without causing gastrointestinal problems like bleeding, as can happen with related analgesics known as nonsteroidal anti-inflammatory drugs (NSAIDs).

NSAIDs include cox-2 inhibitors and common over-the-counter drugs, such as ibuprofen (Advil, Motrin), naproxen (Aleve), and aspirin.

However, cox-2-mediated stomach protection came at a price. In September 2004, Vioxx was pulled from the market after studies linked its long-term use to increased risk for heart attacks. In April 2005, Bextra was pulled because of similar fears, as well as evidence of increased risks for a rare but potentially fatal skin reaction. Celebrex remains the only cox-2 inhibitor sold in the United States, and its label carries a black-box warning detailing potential heart risks.

Dr. Eric J. Topol, director of the Scripps Translational Science Institute in La Jolla, Calif., and Scripps' chief academic officer, was one of the experts who first exposed the problems with Vioxx. He said he doesn't have a problem with cox-2 inhibitors, but he does take issue with Merck's response to emerging data about heart risks.

Topol claims Merck hid evidence about the risk for heart attack associated with Vioxx. "This whole field wouldn't be in the state it's in had it not been for the problems that occurred early on with Vioxx," he said. "They wouldn't have had to make a settlement if they hadn't concealed things."

In December 2005, the editors of the New England Journal of Medicine accused researchers and Merck of withholding key heart risk data that showed up in one of the first large trials of Vioxx; the findings from that trial were published in the journal. Specifically, the editors charged that the study published in November 2000 was submitted to the journal after information about three heart attacks among Vioxx trial participants was deleted by Merck, which funded the study.

In a statement quoted by the Associated Press, Merck said the additional heart attacks "did not materially change any of the conclusions of the article." Merck also said the additional heart attack data was not included in the study, because the heart attacks were reported after Merck's cut-off date for including study data.

Cox-2 inhibitors do work to ease pain, Topol said. "They work at least as well as NSAIDs and, in some patients, better," he said. "Unfortunately, this whole class of drugs has been hit by an outlier."

With the FDA slapping a strong "black box" warning on Celebrex's label, Topol believes the public and doctors are now well-informed about that drug, so they can make appropriate decisions about which patients should or should not receive the medicine.

"Celebrex is safe for most patients, so is Vioxx," Topol asserted. Celebrex, at higher doses, can increase the risk for blood clots, "but the risk never appeared to be as at the same level as Vioxx," he said.

Topol believes people who have heart disease might be at increased risk of heart attack from Celebrex, but there is no real proof of that, he said.

Going without cox-2s may have its downside for patients, too, experts added.

Since Vioxx and Bextra were taken off the market, rates of gastrointestinal events serious enough to require hospitalization have risen significantly, according to a presentation Thursday at the American College of Rheumatology annual meeting, in Boston.

In fact, these complications have risen 21 percent, said a group led by Dr. Gurkirpal Singh, a rheumatologist and a clinical professor of medicine at Stanford University School of Medicine.

Again, when it comes to stomach risks, the decision as to whether to prescribe Celebrex should be made on a case-by-case basis, one expert said.

"There is a lot of confusion over the cox-2 inhibitor Celebrex and the traditional NSAIDs as well," said Dr. Mark Fendrick, a professor of internal medicine at the University of Michigan School of Medicine and professor of health management and policy at the University of Michigan School of Public Health.

For arthritis patients, Fendrick starts treatment with exercise and physical therapy. "I try hard to avoid all drugs and then use topical medications and acetaminophen as first-line medications," he said.

But for patients who need other medication, Fendrick bases his advice on a combination of the individual patient's risk factors for heart disease versus their risk for gastrointestinal problems. "I recommend cox-2 inhibitors like Celebrex for patients who are at risk of gastrointestinal side effects but at low risk for heart disease," he said.

Celebrex has never been shown to be a superior pain reliever and anti-inflammatory drug over any of the other NSAIDs, Fendrick said. "So, alternatives for pain relief and anti-inflammatory effect are just about as good as traditional NSAIDs," he said.

For people who have a high risk of gastrointestinal side effects, such as those with a history of gastrointestinal problems and those taking anticoagulant drugs, Fendrick recommends coupling NSAIDs with stomach-soothing drugs called proton pump inhibitors. These drugs include widely used medications such as Nexium, Prevacid and Prilosec.

More information

There's more on pain relievers at the U.S. National Library of Medicine.

SOURCES: Mark Fendrick, M.D., professor, internal medicine, University of Michigan School of Medicine and professor, health management and policy, University of Michigan School of Public Health, Ann Arbor; Eric J. Topol, M.D., director, Scripps Translational Science Institute, chief academic officer, Scripps Health, and professor of translational genomics, TSRI, senior consultant, Division of Cardiovascular Diseases, Scripps Clinic, La Jolla, Calif.